A significant number of sessile serrated adenomas might not be accurately diagnosed in daily practice

Background/Aims

The diagnosis of hyperplastic polyps (HPs) may involve a conglomeration of subgroups of serrated polyps. The diagnosis of HPs may therefore be revisited if this is sessile serrated adenoma (SSA). The aim of this study was to determine clinically and endoscopically relevant information associated with reclassification to SSA.

Methods

After reviewing the data from 1,372 patients who underwent colonoscopic polypectomy, 49 HPs larger than 10 mm were analyzed in this study. Two gastrointestinal pathologists reclassified each of the original 49 HPs as conventional HPs, SSAs, and others.

Results

Among the 49 initially diagnosed HPs, 18.4% were reclassified into SSAs or mixed polyps. Overall architectural features were useful for the diagnosis of SSA, but cytological features were less useful. The patient and polyp characteristics did not differ between HPs with and without reclassification of the initial pathological diagnosis.

Conclusions

A significant number of SSAs might not be accurately diagnosed in daily clinical practice without any predilection for size, shape, and location. Therefore, when large HPs are diagnosed in clinical practice, it is necessary for physicians to have greater awareness of the diagnosis of SSA and to individualize subsequent surveillance.     

Endoscopic and histologic characteristics of serrated lesions

In recent years , a second pathway for colonic carcinogenesis , distinct from the adenomatous pathway, has been explored. This is referred to as serrated pathway and includes three types of polyp,characterised by a serrated appearance of the crypts:hyperplastic polyps(HP),sessile serrated adenomas(SSA)or lesions,and traditional serrated adenomas.Each lesion has its own genetic,as well as macroscopic and microscopic morphological features.Because of their flat aspect,their detection is easier with chromoendoscopy(carmin indigo or narrow-band imaging).However,as we show in this review,the distinction between SSA and HP is quite difficult.It is now recommended to resect in one piece as it is possible the serrated polyps with a control in a delay depending on the presence or not of dysplasia.These different types of lesion are described in detail in the present review in general population,in polyposis and in inflammatory bowel diseases patients.This review highlights the need to improve characterization and understanding of this way of colorectal cancerogenesis.     

Clinicopathological features,diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma

Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF‐mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to “interval cancers” and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates.     

Endoscopic diagnosis of sessile serrated adenoma/polyp with and without dysplasia/carcinoma

Sessile serrated adenoma/polyps(SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a Cp G island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potentials. Detecting serrated lesions, including SSA/Ps with and without dysplasia/carcinoma, is critical, but SSA/Ps can be difficult to detect, are inconsistently identified by endoscopists and pathologists, and are often incompletely resected. Therefore, SSA/Ps are considered to be major contributors to "interval cancers". If colonoscopists can identify the specific endoscopic characteristics of SSA/Ps, their detection and the effectiveness of colonoscopy may improve. Here, the endoscopic features of SSA/Ps with and without dysplasia/carcinoma, including the characteristics determined using magnifying endoscopy, are reviewed in the context of previous reports. Endoscopically, these subtle polyps are like hyperplastic polyps, because they are slightly elevated and pale. Unlike hyperplastic polyps, SSA/Ps are usually larger than 5 mm, frequently covered by a thin layer called the ‘‘mucus cap', and are more commonly located in the proximal colon. Magnifying narrow-band imaging findings, which include dark spots inside the crypts and varicose microvascular vessels, in addition to the type II-open pit patterns detected using magnifying chromoendoscopy, effectively differentiate SSA/Ps from hyperplastic polyps. The lesions' endoscopic characteristics, which include their(semi)pedunculated morphologies, double elevations, central depressions, and reddishness, and the use of magnifying endoscopy, might help to detect dysplasia/carcinoma within SSA/Ps. Greater awareness may promote further research into improving the detection, identification, and complete resection rates of SSA/Ps with and without dysplasia/carcinoma and reduce the interval cancer rates.     

Frequent somatic mutations of mitochondrial DNA in traditional serrated adenomas but not in sessile serrated adenomas of the colorectum

Background and Aim: Serrated adenomas (SAs), recently subdivided into traditional SAs (TSAs) and sessile SAs (SSAs), are recognized as a distinct form of neoplasia of the colorectum. One of the characteristics of SAs is hypermaturation of the gland epithelium due to the low extent of cell loss by apoptosis. Mutations of mitochondrial DNA (mtDNA) are closely associated with abnormality in apoptosis. We therefore examined mtDNA mutations in colorectal lesions including hyperplastic polyps (HPs), SSAs, TSAs, and carcinomas. Methods: Examined were 25 HPs, 32 SSAs, 19 TSAs, and 138 carcinomas. The D310 region of the mtDNAs was examined by microsatellite assay. Results: mtDNA mutations were detected in none of 25 (0%) HPs, one of 32 (3%) SSAs, six of 19 (32%) TSAs, and eleven of 133 (8%) carcinomas (five of the 138 carcinomas were not informative). The frequency of mtDNA mutations in the TSAs was significantly higher than that in the HPs, SSAs, and carcinomas (P = 0.004, P = 0.008, and P = 0.009, respectively). The frequency of mtDNA mutations in carcinomas was not significantly higher than that in HPs and SSAs (P = 0.14 and P = 0.28, respectively). Conclusion: Our data suggest that mtDNA mutations may play an important role in the development of TSAs and could be used as a genetic marker to aid in the diagnosis of colorectal lesions.     

结直肠锯齿状腺瘤内镜和病理形态特征分析

目的 探讨锯齿状腺瘤（SA）内镜下形态和病理组织学特征.方法 回顾分析南方医院消化内镜中心2002年1月至2005年7月检出的大肠息肉病例,了解SA的检出率、内镜形态、腺管开口分型和病理组织学特征.结果 11894例肠镜检查共检出息肉病例1928例（2811枚）,检出率为16.21%,其中SA 61例（71枚）,检出率为0.51%,占息肉构成比为3.16%.SA直径＞1 cm者占39.44%,明显大于增生性息肉;内镜下表现为有蒂息肉所占的比例（26.76%）高于增生性息肉（13.25%）,但低于腺瘤性息肉（43.95%）.1815枚息肉进行腺管开口分型,SA多表现为Ⅲ型腺管开口（41.67%）,部分表现为Ⅳ型腺管开口（18.33%）,与腺瘤性息肉较接近.SA中度以上异型增生发生率介于管状腺瘤和绒毛状腺瘤之间,并有2.82%的癌变率.结论 SA内镜形态、腺管开口分型和病理学特点提示其本质上与增生性息肉不同,与肿瘤性息肉表现类似,具有恶变潜能.     

结直肠锯齿状腺瘤内镜表现和病理学特征分析

目的探讨锯齿状腺瘤（SA）内镜下表现和病理学特征。方法回顾分析滨州医学院附属医院2000年1月～2008年5月检出的大肠息肉病例,了解SA的检出率、内镜形态和病理学特征。结果8726例肠镜检查共检出大肠息肉1062例（1457枚）,检出率为12．17％,其中SA32例（60枚）,检出率为0．37％,占息肉构成比为3．01％。SA直径〉1cm者占21．63％,明显大于增生性息肉（8．57％）;SA表现为有蒂息肉所占的比例（8．33％）略高于增生性息肉（5．71％）,但都低于腺瘤性息肉（40．84％）。SA癌变率介于管状腺瘤和绒毛状腺瘤之间,接近于管状绒毛状腺瘤。结论SA内镜形态、病理学特点提示SA是兼有增生性息肉形态学特征和腺瘤性息肉组织学特点的息肉,具有恶变潜能.     

Endoscopic diagnosis of sessile serrated polyp: A systematic review

The aim of the present review was to clarify how we should detect and diagnose sessile serrated polyps (SSP) endoscopically. A systematic search was conducted of MEDLINE from January 2004 through March 2018. Nine findings: (i) proximal location; (ii) size >10 mm; (iii) irregular shape; (iv) indistinctive border; (v) cloud‐like surface; (vi) mucus cap; (vii) rim of debris in white‐light endoscopy; (viii) dilated vessels; and (ix) dilated crypts (pits) in image‐enhanced endoscopy were considered to be candidate discriminators of SSP from hyperplastic polyps. Prospective studies in a general setting are warranted to validate the above‐mentioned endoscopic features of SSP during real‐time colonoscopy and to determine whether these features are useful for the differential diagnosis of SSP.     

Sessile serrated adenomas in the proximal colon are likely to be flat,large and occur in smokers

AIM:To examine the epidemiology and the morphology of the proximal sessile serrated adenomas(SSAs).METHODS:We conducted a retrospective study to identify patients with SSAs using a university-based hospital pathology database query from January 2007to April 2011.Data collected included:age,gender,ethnicity,body mass index,diabetes,smoking,family history of colorectal cancer,aspirin,and statin use.We collected data on morphology of SSAs including site(proximal or distal),size,and endoscopic appearance(flat or protuberant).We also compared proximal SSAs to proximal tubular adenomas detected during same time period.RESULTS:One hundred and twenty patients with SSAs were identified:61%were distal and 39%were proximal SSAs.Proximal SSAs were more likely to be flat than distal(100%vs 78%respectively;P=0.0001).Proximal SSAs were more likely to occur in smokers(OR=2.63;95%CI:1.17-5.90;P=0.02)and in patients with family history of colorectal cancer(OR=4.72;95%CI:1.43-15.55;P=0.01)compared to distal.Proximal SSAs were statistically more likely to be≥6 mm in size(OR=2.94;P=0.008),and also more likely to be large(≥1 cm)(OR=4.55;P=0.0005)compared to the distal lesions.Smokers were more likely to have proximal(P=0.02),flat(P=0.01)and large(P=0.007)SSAs compared to non-smokers.Compared to proximal tubular adenomas,proximal SSAs were more likely to be large and occur in smokers.CONCLUSION:Proximal SSAs which accounted for two-fifths of all SSAs were more likely to present as flat lesions,larger SSAs,and were more likely to occur in smokers and in patients with family history of colorectal cancer.Our data has implications for colorectal cancer screening.     

Detection rates for adenomas,serrated polyps and clinically relevant serrated polyps can be easily estimated by individually calculated detection rate ratios

Abstract

Background and aims: Adenoma detection rate (ADR) is a key quality indicator for colonoscopy; however, it is cumbersome to obtain. We investigated if detection rates (DRs) for adenomas, serrated polyps (SPs) and clinically relevant SP (crSPDR) can be accurately estimated by individualized DR ratios (DRRs) in a multicenter primary colonoscopy screening cohort of average-risk individuals.

Methods: DRRs were calculated by dividing DRs for a certain polyp entity by polyp detection rate (PDR) for each endoscopist individually on the basis of his/her first 50 (DRR₅₀) and 100 (DRR₁₀₀) consecutive colonoscopies. DRs were estimated for each endoscopist by multiplying his/her DRR for a certain polyp entity with his/her PDR of subsequent colonoscopies in groups of 50 (DRR₅₀) and 100 (DRR₁₀₀) consecutive colonoscopies. Estimated and actual DRs were compared.

Results: Estimated DRs showed a strong correlation with actual DRs for adenomas (r?=?0.86 and 0.87; each p < .001), SPs (r?=?0.85 and 0.91; each p < .001) and crSPs (r?=?0.82 and 0.86; each p < .001) using DRRs derived from first 50 and 100 consecutive colonoscopies. Corresponding root mean square error (RMSE) between individual estimated and actual DRs using DRR₅₀ and DRR₁₀₀ was 5.3(±4.6)% and 4.5(±4.8)% for adenomas, 5.2(±4.1)% and 3.9(±2.8)% for SP, 3.1(±3.1)% and 2.8(±2.5)% for crSP, respectively. RMSE was not significantly different between DRR₅₀ and DRR₁₀₀ for ADR (p = .445), SPDR (p = .178) and crSP (p = .544).

Conclusions: DR for all relevant polyp entities can be accurately estimated by using individual DRRs. This approach may enable endoscopists to easily track their performance measures in daily routine.     

Comparison of malignant potential between serrated adenomas and traditional adenomas

BACKGROUND: Serrated adenoma is a discrete colorectal epithelial neoplastic lesion that can evolve into colorectal cancer. However, the degree of malignant potential has not been firmly established as yet. The purpose of the present paper was to compare the malignant potential and clinicopathological features between serrated and traditional adenomas. METHODS: A total of 124 serrated adenomas from 116 patients were assessed, and 419 traditional adenomas from 200 were randomly selected. The combination of nuclear dysplasia and serration of > or =20% of crypts was regarded as serrated adenoma. The clinicopathological features of serrated and traditional adenomas were compared, and multivariate analysis performed to confirm whether the malignant potential of serrated adenoma was similar to that of traditional adenoma. RESULTS: The differences in age, sex, total number of adenomas, and synchronous lesions including adenoma with high-grade dysplasia and carcinoma between subjects with and without serrated adenoma were not significant. Serrated adenomas were more frequently located in the rectum and sigmoid colon (P < 0.001), and the average size of serrated adenomas was greater than that of traditional adenomas (P < 0.05). The incidence of malignant lesions including high-grade dysplasia and carcinoma in serrated adenomas was found to be lower than in traditional adenomas (3.2% vs 9.3%, P < 0.05). In the multivariate analysis, adenoma type and polyp size constituted the risk factors for the incidence of high-grade dysplasia and carcinoma. CONCLUSIONS: Serrated adenoma is a premalignant lesion, but it has a lower potential for the development of malignancy than traditional adenomas.     

Serrated polyps of the colon and rectum: Remove or not?

In recent years, the serrated neoplasia pathway where serrated polyps arise as a colorectal cancer has gained considerable attention as a new carcinogenic pathway. Colorectal serrated polyps are histopathologically classified into hyperplastic polyps(HPs), sessile serrated lesions, and traditional serrated adenomas; in the serrated neoplasia pathway, the latter two are considered to be premalignant. In western countries, all colorectal polyps, including serrated polyps, apart from diminutive rectosigmoid HPs are removed. However, in Asian countries, the treatment strategy for colorectal serrated polyps has remained unestablished. Therefore, in this review, we described the clinicopathological features of colorectal serrated polyps and proposed to remove HPs and sessile serrated lesions ≥ 6 mm in size, and traditional serrated adenomas of any size.     

Sessile serrated adenoma/polyp showed rapid malignant transformation in the final 13 months

Based on the concept of the adenoma-carcinoma sequence, most colorectal cancers are considered to arise from conventional adenomas. However, recent studies suggested that a subset of colorectal cancers develop through the serrated neoplastic pathway. It has also been documented that serrated polyps can rapidly transform into invasive cancers even when they are small in size. We now describe a case of a sessile serrated adenoma/polyp which had been followed up for 4 years but eventually showed rapid transformation into an advanced cancer accompanied by a remarkable morphological change within only 13 months. Retrospective genetic and epigenetic analyses showed microsatellite instability, CpG island methylator phenotype-positive, and BRAF mutation in the lesion, suggesting the tumor had developed through the serrated neoplastic pathway. This case may provide valuable information about the natural history of sessile serrated adenoma/polyps which eventually progress to advanced cancers.